Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson's Disease
Recommended Citation
Ranxhi B, Bangash ZR, Chbihi ZM, Qadri Z, Islam NN, Todi SV, LeWitt PA, and Tsou WL. Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson's Disease. NPJ Parkinsons Dis 2025;11(1):231.
Document Type
Article
Publication Date
8-6-2025
Publication Title
NPJ Parkinsons Dis
Abstract
Parkinson's Disease (PD) is a neurodegenerative disorder characterized by α-synuclein accumulation and aggregation, leading to disrupted cellular homeostasis, impaired mitochondrial function, and neuroinflammation, ultimately causing neuronal death. Recent biomarker studies reveal elevated serum levels of L-ornithine-derived polyamines correlating with PD progression and clinical subtypes, though their precise role in PD pathology remains unclear. We investigated the impact of polyamine-interconversion enzymes (PAIEs) on α-synucleinopathy in a Drosophila melanogaster model of PD, evaluating key degenerative features such as lifespan, locomotor function, tissue integrity, and α-synuclein accumulation. Knockdown of ornithine decarboxylase 1 (ODC1), spermidine synthase (SRM), and spermine oxidase (SMOX) reduced α-synuclein toxicity, while suppression of spermidine/spermine N1-acetyltransferase 1 (SAT1) and spermine synthase (SMS) exacerbated it. Conversely, overexpressing SAT1 or SMOX significantly reduced α-synuclein toxicity, highlighting their potential role in PD. These findings underscore the critical role of polyamine pathways in modulating α-synuclein toxicity, offering novel therapeutic targets for PD.
PubMed ID
40770267
Volume
11
Issue
1
First Page
231
Last Page
231
